Evaluation of pentacyclic triterpenes found in Perilla frutescens for inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate

• Published in: Oncotarget Vol. 6; no. 36; pp. 39292 - 39306
• Main Authors: Cho, Jiyoon, Tremmel, Lisa, Rho, Okkyung, Camelio, Andrew M, Siegel, Dionicio, Slaga, Thomas J, DiGiovanni, John
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 17.11.2015
• Subjects: Animals; Drug Interactions; Female; Mice; Mice, Inbred ICR; Pentacyclic Triterpenes - isolation & purification; Pentacyclic Triterpenes - pharmacology; Perilla frutescens - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Research Paper; Signal Transduction; Skin Neoplasms - chemically induced; Skin Neoplasms - pathology; Skin Neoplasms - prevention & control; Tetradecanoylphorbol Acetate - pharmacology; pentacyclic triterpenes; skin tumor promotion; chemoprevention; P. frutescens; ursolic acid
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.5751

A series of pentacyclic tritperpenes found in Perilla frutescens (P. frutescens), including ursolic acid (UA), oleanolic acid (OA), corosolic acid (CA), 3-epi-corosolic acid (3-epiCA), maslinic acid (MA), and 3-epi-maslinic acid (3-epiMA) were evaluated for their effects on epidermal cell signaling, proliferation, and skin inflammation in relation to their ability to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) and compared to UA as the prototype compound. All compounds were given topically 30 min prior to each TPA application and significantly inhibited skin tumor promotion. 3-epiCA and MA were significantly more effective than UA at inhibiting tumor development. All of these compounds significantly inhibited epidermal proliferation induced by TPA, however, CA, 3-epiCA and MA were more effective than UA. All compounds also reduced skin inflammation (assessed by infiltration of mast cells and T-cells) and inflammatory gene expression induced by TPA, however, 3-epiCA and MA were again more effective than UA. The greater ability of 3-epiCA and MA to inhibit skin tumor promotion was associated with greater reduction of Cox-2 and Twist1 proteins and inhibition of activation (i.e., phosphorylation) of IGF-1R, STAT3 and Src. Further study of these compounds, especially 3-epiCA and MA, for chemopreventive activity in other cancer model systems is warranted.